TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17009	51250;51251;51252	chr2:178611104;178611103;178611102	chr2:179475831;179475830;179475829
N2AB	15368	46327;46328;46329	chr2:178611104;178611103;178611102	chr2:179475831;179475830;179475829
N2A	14441	43546;43547;43548	chr2:178611104;178611103;178611102	chr2:179475831;179475830;179475829
N2B	7944	24055;24056;24057	chr2:178611104;178611103;178611102	chr2:179475831;179475830;179475829
Novex-1	8069	24430;24431;24432	chr2:178611104;178611103;178611102	chr2:179475831;179475830;179475829
Novex-2	8136	24631;24632;24633	chr2:178611104;178611103;178611102	chr2:179475831;179475830;179475829
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCT
• RefSeq wild type template codon: AGA
• Domain: Ig-111
• Domain position: 55
• Structural Position: 135
• Q(SASA): 0.1924
• Predicted PPI site: N

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
S/P	None	None	1.0	D	0.818	0.527	0.3571064206	gnomAD-4.0.0	2.05369E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.6995E-06	0	0

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
S/A	0.0851	likely_benign	0.0915	benign	-0.435	Destabilizing	0.997	D	0.479	neutral	N	0.509285097	None	None	N
S/C	0.1112	likely_benign	0.0975	benign	-0.314	Destabilizing	1.0	D	0.779	deleterious	D	0.542548489	None	None	N
S/D	0.4947	ambiguous	0.4935	ambiguous	-1.524	Destabilizing	0.999	D	0.657	neutral	None	None	None	None	N
S/E	0.5482	ambiguous	0.528	ambiguous	-1.375	Destabilizing	0.999	D	0.619	neutral	None	None	None	None	N
S/F	0.1451	likely_benign	0.1369	benign	-0.283	Destabilizing	1.0	D	0.804	deleterious	N	0.514004079	None	None	N
S/G	0.134	likely_benign	0.1348	benign	-0.807	Destabilizing	0.999	D	0.543	neutral	None	None	None	None	N
S/H	0.2999	likely_benign	0.263	benign	-1.473	Destabilizing	1.0	D	0.796	deleterious	None	None	None	None	N
S/I	0.1604	likely_benign	0.1524	benign	0.489	Stabilizing	1.0	D	0.782	deleterious	None	None	None	None	N
S/K	0.6365	likely_pathogenic	0.5964	pathogenic	-0.553	Destabilizing	0.999	D	0.642	neutral	None	None	None	None	N
S/L	0.0964	likely_benign	0.0962	benign	0.489	Stabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	N
S/M	0.1897	likely_benign	0.1821	benign	0.522	Stabilizing	1.0	D	0.792	deleterious	None	None	None	None	N
S/N	0.1736	likely_benign	0.1694	benign	-1.143	Destabilizing	0.999	D	0.621	neutral	None	None	None	None	N
S/P	0.8198	likely_pathogenic	0.8079	pathogenic	0.217	Stabilizing	1.0	D	0.818	deleterious	D	0.647668156	None	None	N
S/Q	0.4887	ambiguous	0.4581	ambiguous	-0.894	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
S/R	0.5135	ambiguous	0.4717	ambiguous	-0.933	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
S/T	0.0804	likely_benign	0.0815	benign	-0.725	Destabilizing	0.999	D	0.522	neutral	N	0.497302033	None	None	N
S/V	0.1689	likely_benign	0.1669	benign	0.217	Stabilizing	1.0	D	0.769	deleterious	None	None	None	None	N
S/W	0.2943	likely_benign	0.2703	benign	-0.702	Destabilizing	1.0	D	0.79	deleterious	None	None	None	None	N
S/Y	0.1435	likely_benign	0.1348	benign	-0.237	Destabilizing	1.0	D	0.801	deleterious	D	0.532559265	None	None	N

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.